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Researchers with the Perinatal Institute at Cincinnati Children’s
Hospital Medical Center have expertise in the social sciences, public
health, epidemiology, process and quality improvement, health care
economics and advocacy policy, as well as the more traditional avenues
of basic science, translational research and clinical trials. Insights
from our research can be directly applied to the clinical challenges
faced by infants during the perinatal period.
James M. Greenberg, MD Co-Director, Perinatal Institute
investigates the developmental biology of pulmonary vascular development, including how vascular endothelial growth factor (VEGF) mediates pulmonary vascular, lymphatic and airway development. He studies how VEGF mediates organization of pulmonary vasculature during late fetal life as well as how certain proteins implicated in axonal guidance during central nervous system development also direct developmental processes in the lung.
Co-Director, Perinatal Institute
Director, Division of Neonatology
Professor, UC Department of Pediatrics
Neonatal chronic lung disease; late preterm infant
MD: University of Illinois College of Medicine, Chicago, IL, 1977-1981.
Pediatric Internship and Residency: University of Minnesota Hospital and Clinic, Minneapolis, MN, 1981-1984. Chief Resident, Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis, MN, 1984.
Fellowship: Immunology/Neonatology, University of Minnesota Hospital and Clinic, Minneapolis, MN, 1985-1987; 1988-1989; visiting scientist, Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, England.
Certification: American Board of Pediatrics, 1988; subspecialty board, Neonatal/Perinatal Medicine, 1989.
Binder S, Hill K, Meinzen-Derr J, Greenberg JM, Narendran V. Increasing VLBW Deliveries at Subspecialty Perinatal Centers via Perinatal Outreach. Pediatrics. 2011 Mar;127(3):487-93.
Kulkarni RM, Herman A, Ikegami M, Greenberg JM, Akeson AL. Lymphatic ontogeny and effect of hypoplasia in developing lung. Mech Dev. 2011 Jan-Feb;128(1-2):29-40.
Kulkarni RM, Greenberg JM, Akeson AL. NFATc1 regulates lymphatic endothelial development. Mech Dev. 2009 May-Jun;126(5-6):350-65.
Mallory BP, Mead TJ, Wiginton DA, Kulkarni RM, Greenberg JM, Akeson AL. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res. 2006 Jul-Sep;72(1-2):62-73.
Preciado DA, Rutter MJ, Greenberg JM, Bahado-Singh R, Lambers D, Willging JP. Intrapartum management of severe fetal airway obstruction. J Otolaryngol. 2004 Oct;33(5):283-8.
Akeson AL, Cameron JE, Le Cras TD, Whitsett JA, Greenberg JM. Vascular endothelial growth factor-A induces prenatal neovascularization and alters bronchial development in mice. Pediatr Res. 2005 Jan;57(1):82-8.
Greenberg JM, Thompson FY, Brooks SK, Shannon JM, Akeson AL. Slit and robo expression in the developing mouse lung. Dev Dyn. 2004 Jun;230(2):350-60.
Le Cras TD, Spitzmiller RE, Albertine KH, Greenberg JM, Whitsett JA, Akeson AL. VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice. Am J Physiol Lung Cell Mol Physiol. 2004 Jul;287(1):L134-42.
Akeson AL, Greenberg JM, Cameron JE, Thompson FY, Brooks SK, Wiginton D, Whitsett JA. Temporal and spatial regulation of VEGF-A controls vascular patterning in the embryonic lung. Dev Biol. 2003 Dec 15;264(2):443-55.
Greenberg JM, Thompson FY, Brooks SK, Shannon JM, McCormick-Shannon K, Cameron JE, Mallory BP, Akeson AL. Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung. Dev Dyn. 2002 Jun;224(2):144-53.
Louis J. Muglia, MD, PhD Co-Director, Perinatal Institute
Director, Center for Prevention of Preterm Birth
Visit the Muglia Lab
Dr. Muglia has pioneered the in vivo analyses of regulation of the endocrine stress response and the molecular pathways leading to birth using novel genetically altered mutant mice. These studies have elucidated the importance of corticotropin-releasing hormone, glucocorticoids, and prostaglandins in neuroendocrine modulation, behavior, and perinatal adaptation. These studies have evolved over the last decade to specifically focus on the mechanisms controlling the timing for birth in humans using genetics and comparative genomics. The composition of the biological clock metering the duration of human gestation remains a central question in reproductive biology. The goal of the Muglia Laboratory is to understand the molecular timing machinery comprising this biological clock to prevent or better treat human preterm labor and delivery.
Among Dr. Muglia’s achievements are more than 180 publications and many awards, including a Burroughs Wellcome Fund Career Development Award in the biomedical sciences, the Society of Pediatric Research Young Investigator Award, and election to the American Society for Clinical Investigation and Association of American Physicians. In 2010, Dr. Muglia was elected to fellow in the American Association for the Advancement of Science. He is an active member of the Society for Pediatric Research, Society for Neuroscience, and the Lawson Wilkins Pediatric Endocrine Society. Dr. Muglia currently serves as chair of the Board of Scientific Counselors for the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. In 2013, Dr. Muglia was elected to membership in the Institute of Medicine of the National Academies.
BS: University of Michigan, Ann Arbor, MI, 1981.
PhD: University of Chicago, Chicago, IL, 1986.
MD: University of Chicago, Chicago, IL, 1988.
Plunkett J, Doniger S, Orabona G, Morgan T, Haataja R, Hallman M, Puttonen H, Menon R, Kuczynski E, Norwitz E, Victoria Snegovskikh V, Palotie A, Peltonen L, Fellman V, DeFranco EA, Chaudhari BP, McGregor TL, McElroy JJ, Oetjens MT, Teramo K, Boreck I, Fay J, Muglia L. An evolutionary genomic approach to identify genes involved in human birth timing. PLoS Genetics. 2011; 7: e1001365.
Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med. 2010; 362: 529-535.
Kolber BJ, Boyle MP, Wieczorek L, Kelley CL, Kelley CL, Onwuzurike CC, Nettles SA, Vogt SK, Muglia LJ. Transient early-life forebrain corticotropin-releasing hormone elevation causes long-lasting anxiogenic and despair-like changes in mice. J Neurosci. 2010; 30: 2571-2581.
Plunkett J, Feitosa MF, Trusgnich M, Wangler MF, Palomar L, Kistka ZA-F, DeFranco EA, Shen TT, Stormo EAD, Puttonen H, Hallman M, Haataja R, Luukkonen A, Fellman V, Peltonen L, Palotie A, Daw EW, An P, Teramo K, Borecki I, Muglia LJ. Mother’s genome or maternally-inherited genes acting in the fetus influence gestational age in familial preterm birth. Human Heredity. 2009; 68: 209-219.
Kolber BJ, Roberts MS, Howell MP, Wozniak DF, Sands MS, Muglia LJ. Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc Natl Acad Sci USA. 2008; 105: 12004 - 12009.
Roizen J, Asada M, Tong M, Tai H-H, Muglia LJ. Preterm birth without progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice. Mol Endocrinol. 2008; 22: 105-112.
Kistka Z A-F, Palomar P, Lee KA, Boslaugh SE, Wangler MF, Cole FS, DeBaun MR, Muglia LJ. Racial disparity in the frequency of recurrence of preterm birth. Am J Obstet Gynecol. 2007; 196: 131.e1-131.e6.
Bethin KE, Nagai Y, Sladek R, Asada M, Sadovsky Y, Hudson TJ, Muglia LJ. Microarray analysis of uterine gene expression in mouse and human pregnancy. Mol Endocrinol. 2003; 17: 1454-1469.
Gross G, Imamura T, Luedke C, Vogt SK, Olson LM, Nelson DM, Sadovsky Y, Muglia LJ. Opposing actions of prostaglandins and oxytocin determine the onset of murine labor. Proc. Natl. Acad. Sci. USA. 1998; 95: 11871-11875.
Muglia LJ, Jacobson L, Dikkes P, Majzoub JA. Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need. Nature. 1995; 373:427-432.
Maternal Temperament, Stress, Inflammation and Preterm Birth. Multi-PI. NIH/NICHD. Sep 2013-Aug 2017.
March of Dimes Prematurity Research Center Ohio Collaborative. Coordinating PI. March of Dimes. Jul 2013-Jun 2018.
Jeffrey A. Whitsett, MD Co-Director, Perinatal Institute
Chief, Section of Neonatology, Perinatal and Pulmonary Biology
Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy
Visit the Whitsett Lab.
Jeffrey A. Whitsett, MD, is chief of the Section of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children's Hospital Medical Center.
Dr. Whitsett received his medical degree from Columbia University, in New York, and has been a faculty member since 1977. He is internationally known for his research in pulmonary medicine, as well as for his clinical expertise in neonatology.
Dr. Whitsett has made a series of groundbreaking contributions in pulmonary medicine. His major pioneering work has been on surfactant proteins A, B, C and D, cloning their genes, and clarifying their roles in lung development.
Throughout his career, Dr. Whitsett has had the remarkable ability to move from molecular biology, to animal models, to diagnosis and therapy of human disease. He played a critical role in making surfactant protein replacement a routine tool for treating immature lungs and respiratory distress syndrome in premature infants. His laboratory has contributed to the identification of a number of genes critical for lung formation and function. Mutations in genes regulating surfactant homeostasis were shown to cause acute and chronic lung disease in infants and adults.
Dr. Whitsett is a member of the Institute of Medicine, National Academy of Sciences and is the recipient of the Mead Johnson Award, a National Institutes of Health (NIH) Merit Award, the first Julius Comroe Lectureship in Pulmonary Research from FASEB, the William Cooper Procter Award from Cincinnati Children's, the Amberson Lecture Award of the American Thoracic Society, the prestigious Daniel Drake Medal for scientific contributions from the University of Cincinnati College of Medicine, the International Arvo Ylppö Medal from the Finnish Foundation for Pediatric Research and the Grand Hamdan International Award on Neonatal Medicine from the United Arab Emirates.
Dr. Whitsett is the author of more than 400 papers in both the basic science and clinical literature.
MD: Columbia University, New York, NY, 1973.
Residency: Pediatrics, Mt. Sinai Hospital, New York City, 1974 to 1976.
Fellowship: Neonatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 1976 to 1977.
Sivaprasad U, Askew DJ, Ericksen MB, Gibson AM, Stier MT, Brandt EB, Bass SA, Daines MO, Chakir J, Stringer KF, Wert SE, Whitsett JA, Le Cras TD, Wills-Karp M, Silverman GA, Khurana Hershey GK. A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma. J Allergy Clin Immunol. 2011 Jan;127(1):254-61, 261.e1-6.
Lin SC, Wani MA, Whitsett JA, Wells JM. Klf5 regulates lineage formation in the pre-implantation mouse embryo. Development.2010 Dec;137(23):3953-63.
Suzuki T, Sakagami T, Young LR, Carey BC, Wood RE, Luisetti M, Wert SE, Rubin BK, Kevill K, Chalk C, Whitsett JA, Stevens C, Nogee LM, Campo I, Trapnell BC. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1292-304.
Wang IC, Zhang Y, Snyder J, Sutherland MJ, Burhans MS, Shannon JM, Park HJ, Whitsett JA, Kalinichenko VV. Increased expression of FoxM1 transcription factor in respiratory epithelium inhibits lung sacculation and causes Clara cell hyperplasia. Dev Biol. 2010 Nov 15;347(2):301-14.
Perl AK, Riethmacher D, Whitsett JA. Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis. Am J Respir Crit Care Med. 2010 Sep 24.
Tompkins DH, Besnard V, Lange AW, Keiser AR, Wert SE, Bruno MD, Whitsett JA. Sox2 Activates Cell Proliferation and Differentiation in the Respiratory Epithelium. Am J Respir Cell Mol Biol. 2010 Sep 20.
Meyer SE, Hasenstein JR, Baktula A, Velu CS, Xu Y, Wan H, Whitsett JA, Gilks CB, Grimes HL. Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival. Am J Pathol. 2010 Sep;177(3):1503-13.
Xu Y, Zhang M, Wang Y, Kadambi P, Dave V, Lu LJ, Whitsett JA. A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics. 2010 Jul 26;11:451.
Sakagami T, Beck D, Uchida K, Suzuki T, Carey BC, Nakata K, Keller G, Wood RE, Wert SE, Ikegami M, Whitsett JA, Luisetti M, Davies S, Krischer JP, Brody A, Ryckman F, Trapnell BC. Patient-derived granulocyte/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates. Am J Respir Crit Care Med. 2010 Jul 1;182(1):49-61.
Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, Wills-Karp M, Whitsett JA. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010 Jun 1;184(11):6133-41.
Bruce J. Aronow, PhD Co-director, Computational Medicine Center
Co-director, Computational Medicine Center
Dr. Aronow's research is devoted to unraveling both the role and mechanism by which the functional capabilities of the human genome shape human health and our ability to adapt to stressful challenges. His lab is using a variety of available structural and functional genomic and biological systems descriptive data to form models of how biological systems assemble, adapt and become impaired in disease. The lab's overall hypothesis is that by interconnecting as much experimental and observational information as possible, we can gain new insights into the mechanisms by which different biological systems can achieve health or healthy adaptation, or undergo disease processes. More specific, with the co-leadership of Anil Jegga, DVM, the lab is identifying genetic features that control gene expression including cis-elements, trans factors and microRNAs, which normally work together in extended cell, tissue, organ and systems networks to enable development and homeostasis. Alterations of these features can alter phenotypes and increase or decrease disease. Some of the lab's work includes the identification of conserved, diverged and evolved cis-element clusters that are acted on by transcription and chromatin proteins. The lab has developed a Web-based tool called GenomeTraFaC that at present allows discovery of shared cis-elements in conserved non-coding sequences of mice and humans.
Barnes MG, Grom AA, Thompson SD, Griffin TA, Pavlidis P, Itert L, et al. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis and rheumatism. 2009 Jul;60(7):2102-12.
Qu XA, Gudivada RC, Jegga AG, Neumann EK, Aronow BJ. Inferring novel disease indications for known drugs by semantically linking drug action and disease mechanism relationships. BMC Bioinformatics. 2009 May;10 Suppl 5:S4.
Gu Y, Harley IT, Henderson LB, Aronow BJ, Vietor I, Huber LA, et al. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature. 2009 Apr 23;458(7241):1039-42.
Nishijo K, Chen QR, Zhang L, McCleish AT, Rodriguez A, Cho MJ, et al. Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma. Cancer Res. 2009 Apr 1;69(7):2902-11.
Chen J, Aronow BJ, Jegga AG. Disease candidate gene identification and prioritization using protein interaction networks. BMC Bioinformatics. 2009 Feb;10:73.
Shen H, Powers N, Saini N, Comstock CE, Sharma A, Weaver K, et al. The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res. 2008 Dec 15;68(24):10154-62.
Brunskill EW, Aronow BJ, Georgas K, Rumballe B, Valerius MT, Aronow J, et al. Atlas of gene expression in the developing kidney at microanatomic resolution. Developmental cell. 2008 Nov;15(5):781-91.
Mahller YY, Sakthivel B, Baird WH, Aronow BJ, Hsu YH, Cripe TP, et al. Molecular analysis of human cancer cells infected by an oncolytic HSV-1 reveals multiple upregulated cellular genes and a role for SOCS1 in virus replication. Cancer Gene Ther. 2008 Nov;15(11):733-41.
Kucherlapati MH, Yang K, Fan K, Kuraguchi M, Sonkin D, Rosulek A, et al. Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the cecum and proximal colon. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15493-8.
Gudivada RC, Qu XA, Chen J, Jegga AG, Neumann EK, Aronow BJ. Identifying disease-causal genes using Semantic Web-based representation of integrated genomic and phenomic knowledge. J Biomed Inform. 2008 Oct;41(5):717-29.
Samantha A. Brugmann, PhD Member, Division of Plastic Surgery
is a developmental biologist who aims to understand craniofacial development and elucidate the molecular basis for diseases that affect the craniofacial complex. Furthermore, Dr. Brugmann attempts to understand the forces that help pattern the face during normal and abnormal development she utilizes various model systems with unique facial morphologies.
Visit the Brugmann Lab.
Member, Division of Plastic Surgery
Assistant Professor, UC Department of Surgery
Samantha A. Brugmann, PhD, is an assistant professor of pediatrics in the Divisions of Plastic Surgery and Developmental Biology within the University of Cincinnati College of Medicine. She received her BS in cell and molecular biology from Tulane University in New Orleans, LA. She then obtained her PhD in genetics from George Washington University in Washington, DC where she studied cranial sensory placode development in Xenopus laevis. She performed her postdoctoral fellowship at Stanford University where her research focused on craniofacial development. While at Stanford she received a Ruth L. Kirschstein National Research Service Awards for Individual Postdoctoral Fellows (F32), a Pediatric Research Fund-Child Health Research Program Grant and a NIH Pathway to Independence Award (K99/R00). She joined Cincinnati Children’s Hospital Medical Center in January 2011 to study craniofacial development and disease.
Chang CF, Schock EN, Attia A, Stottmann RW, Brugmann SA. The ciliary baton: orchestrating neural crest development. Current Topics in Developmental Biology. In press.
Brugmann SA, Wells JM. Building additional complexity to in vitro-derived intestinal tissues. Stem Cell Res Ther. 2013;4 Suppl 1:S1.
Liu H, Lan Y, Xu , Chang CF, Brugmann SA, Jiang R. Odd-skipped related-1 controls neural crest chondrogenesis during tongue development. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18555-60.
Chang CF, Schock EN, O’Hare EA, Dodgson J, Cheng HH, Muir WM, Edelmann RE, Delany ME, Brugmann SA. The cellular and molecular etiology of the craniofacial defects in the avian ciliopathic mutant, talpid2. Development. 2014 Aug;141(15):3003-12.
Rada-Iglesias A, Bajpai R, Prescott S, Brugmann SA, Swigut T, Wysocka J. Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest. Cell Stem Cell. 2012 Nov 2;11(5):633-48.
Lenton K, James AW, Manu A, Brugmann SA, Birker D, Nelson ER, Leucht P, Helms JA, Longaker MT. Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. Genesis. 2011 Oct;49(10):784-96.
Powder KE, Ku YC, Brugmann SA, Veile RA, Renaud NA, Helms JA, Lovett M. A cross-species analysis of microRNAs in the developing avian face. PLoS One. 2012;7(4):e35111.
Kenneth J. Campbell, PhD
studies the molecular genetic control of mouse forebrain development with a particular focus on the generation of neuronal diversity in the ventral telencephalon.
Molecular genetic control of mammalian forebrain development
MS: University of Toronto, Toronto, Canada, 1990.
PhD: University of Lund, Lund, Sweden, 1994.
Postdoctoral Fellow: Skirball Institute, NYU Med Center, 1995-97.
Waclaw RR, Wang B, Pei Z, Ehrman LA, Campbell K. Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates. Neuron. 2009;63:451-65.
Wang B, Waclaw RR, Allen ZJ II, Guillemot F, Campbell K. Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon. Neural Development. 2009;4:5.
Waclaw RR, Allen Z, Bell SM, Erdelyi F, Szabo G, Potter SS, Campbell K. The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons. Neuron. 2006;49:503-16.
Campbell K. Cortical neuron specification: it has its time and place. Neuron. 2005;46:373-6.
Waclaw RR, Wang B, Campbell K. The homeobox gene Gsh2 is required for retinoid production in the embryonic mouse telencephalon. Development. 2004;131:4013-20.
Stenman J, Yu RT, Evans RM, Campbell K. Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the mouse telencephalon. Development. 2003;130:1113-22.
Stenman J, Toresson H, Campbell K. Identification of two distinct progenitor populations in the lateral ganglionic eminence: Implications for striatal and olfactory bulb neurogenesis. Journal of Neuroscience. 2003;23:167-74.
Sang-Wook Cha, PhD
investigates how Wnt/Planar Cell Polarity (PCP) signaling between lateral plate mesoderm (LPM) and endoderm regulates apicobasal polarity (ABP) of intestinal epithelium and controls radial-intercalation and gut elongation. Dr. Cha uses both amphibian and mouse/human organoids as the model systems.